Yehia Ali R., Jeandupeux Dominique, Alonso Francisco, Guevara Michael R.
Department of Physiology and Centre for Nonlinear Dynamics in Physiology and Medicine, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Chaos. 1999 Dec;9(4):916-931. doi: 10.1063/1.166465.
The transmembrane potential of a single quiescent cell isolated from rabbit ventricular muscle was recorded using a suction electrode in whole-cell recording mode. The cell was then driven with a periodic train of current pulses injected into the cell through the same recording electrode. When the interpulse interval or basic cycle length (BCL) was sufficiently long, 1:1 rhythm resulted, with each stimulus pulse producing an action potential. Gradual decrease in BCL invariably resulted in loss of 1:1 synchronization at some point. When the pulse amplitude was set to a fixed low level and BCL gradually decreased, N+1:N rhythms (N>/=2) reminiscent of clinically observed Wenckebach rhythms were seen. Further decrease in BCL then yielded a 2:1 rhythm. In contrast, when the pulse amplitude was set to a fixed high level, a period-doubled 2:2 rhythm resembling alternans rhythm was seen before a 2:1 rhythm occurred. With the pulse amplitude set to an intermediate level (i.e., to a level between those at which Wenckebach and alternans rhythms were seen), there was a direct transition from 1:1 to 2:1 rhythm as the BCL was decreased: Wenckebach and alternans rhythms were not seen. When at that point the BCL was increased, the transition back to 1:1 rhythm occurred at a longer BCL than that at which the {1:1-->2:1} transition had initially occurred, demonstrating hysteresis. With the BCL set to a value within the hysteresis range, injection of a single well-timed extrastimulus converted 1:1 rhythm into 2:1 rhythm or vice versa, providing incontrovertible evidence of bistability (the coexistence of two different periodic rhythms at a fixed set of stimulation parameters). Hysteresis between 1:1 and 2:1 rhythms was also seen when the stimulus amplitude, rather than the BCL, was changed. Simulations using numerical integration of an ionic model of a single ventricular cell formulated as a nonlinear system of differential equations provided results that were very similar to those found in the experiments. The steady-state action potential duration restitution curve, which is a plot of the duration of the action potential during 1:1 rhythm as a function of the recovery time or diastolic interval immediately preceding that action potential, was determined. Iteration of a finite-difference equation derived using the restitution curve predicted the direct {1:1<-->2:1} transition, as well as bistability, in both the experimental and modeling work. However, prediction of the action potential duration during 2:1 rhythm was not as accurate in the experiments as in the model. Finally, we point out a few implications of our findings for cardiac arrhythmias (e.g., Mobitz type II block, ischemic alternans). (c) 1999 American Institute of Physics.
采用吸力电极以全细胞记录模式记录从兔心室肌分离出的单个静息细胞的跨膜电位。然后通过同一个记录电极向细胞内注入周期性的电流脉冲串来驱动该细胞。当脉冲间期或基本周期长度（BCL）足够长时，会产生1:1节律，每个刺激脉冲都会引发一个动作电位。BCL逐渐减小必然会在某个时刻导致1:1同步性丧失。当将脉冲幅度设置为固定的低水平且BCL逐渐减小时，会出现类似于临床观察到的文氏节律的N + 1:N节律（N≥2）。BCL进一步减小则会产生2:1节律。相比之下，当将脉冲幅度设置为固定的高水平时，在出现2:1节律之前会出现类似于交替节律的周期加倍的2:2节律。当将脉冲幅度设置为中间水平（即介于出现文氏节律和交替节律的幅度之间）时，随着BCL减小，会直接从1:1节律转变为2:1节律：未观察到文氏节律和交替节律。当此时BCL增大时，恢复到1:1节律的转变发生时的BCL比最初发生{1:1→2:1}转变时的BCL更长，这表明存在滞后现象。当BCL设置在滞后范围内的值时，适时注入单个额外刺激会将1:1节律转变为2:1节律，反之亦然，这提供了双稳性的无可争议的证据（在一组固定的刺激参数下两种不同的周期性节律共存）。当改变刺激幅度而非BCL时，也观察到了1:1和2:1节律之间的滞后现象。使用将单个心室细胞的离子模型表述为微分方程非线性系统的数值积分进行的模拟得到的结果与实验结果非常相似。确定了稳态动作电位时程恢复曲线，该曲线是1:1节律期间动作电位时程作为紧接该动作电位之前的恢复时间或舒张间期的函数的图。使用恢复曲线推导的有限差分方程的迭代在实验和建模工作中都预测了直接的{1:1↔2:1}转变以及双稳性。然而，实验中对2:1节律期间动作电位时程的预测不如模型中准确。最后，我们指出了我们的发现对心律失常（如莫氏Ⅱ型阻滞、缺血性交替）的一些启示。（c）1999美国物理研究所。
